Abstract: :
Purpose: To characterize homozygote and heterozygote memberswithin three nuclear consanguineous families carrying the sameR91W mutation in the RPE65 gene based on visual function, fullfield electroretinography (ERG) and pupillometry (PM).Methods:The R91W mutation was confirmed in 11 homozygotes and 9 heterozygoteswhounderwent complete ophthalmologic examination and when possiblevisual field, fluorescein angiography (FA), ERG and PM.Results:All affected members had useful vision in the first decade oflife and progressively lost vision in the third decade of lifeto the point of disability. Eleven homozygotes were aged 18to 55 years with acuities ranging from CF to NLP. All had nystagmus.Retinal findings were subdivided into two classes. Class 1 includedmid-peripheral drusen-like deposits, absence of pigmented clumps.Class 2 included mid peripheral pigmented clumps and absenceof drusen-like deposits. Patients class 1 had better visionthan patients class 2. Mean age in class 1 was 29±12.02years and 47±5.45 years in class 2 (p=0.03). ERG obtainedin the 8 homozygotes showed absence of photopic and scotopicresponses. Evaluation of the pupillary light reflex revealeddiminished contraction amplitude, prolonged latency times anddecreased contraction velocity in 3 homozygotes with poor vision.One additional homozygote had subnormal reactivity with onlya minimal prolongation of the pupillary latency time. Elevenheterozygotes were aged 34 to 86. All had normal vision exceptone who was diabetic and had high myopia and age-related cataract.None had nystagmus. Visual acuities range from 20/200 to 20/20.Funduscopy and ERG were normal in 2 heterozygotes tested. Pupillometrywas normal in 2 heterozygotes. A third heterozygote (diabetic)had a minimally prolonged pupillary latency time in both eyes.Conclusions: The significant difference in age between thetwo retinal classes suggested that they may represent a continuumin the evolution of the disease. Homozygotes of both class 1and 2 showed a complete loss of ERG responses and an abnormalpupillary light reflex. All heterozygotes showed normal visualfunction including ERG and pupillometry except for one diabeticpatient.